Phospho-PERK (Thr980) Recombinant Rabbit mAb (S-4247)

Phospho-PERK (Thr980) is the activated form of protein kinase R-like endoplasmic reticulum kinase (PERK) phosphorylated at threonine residue 980, and this event represents a hallmark molecular indicator of the PERK signaling branch activation within the unfolded protein response (UPR). PERK is a type I transmembrane protein localized on the endoplasmic reticulum membrane, with its N-terminal domain facing the ER lumen to sense accumulated unfolded proteins and its C-terminal kinase domain exposed to the cytoplasmic side; upon ER stress, PERK undergoes autophosphorylation through dimerization, among which Thr980 is located within the activation loop and its phosphorylation is essential for the full induction of PERK kinase activity. Activated Phospho-PERK (Thr980) subsequently phosphorylates its downstream substrate, eukaryotic translation initiation factor 2α at Ser51 (i.e., eIF2α), thereby reducing the global protein synthesis burden to alleviate ER protein folding load, while preferentially upregulating the expression of transcription factors such as ATF4 to promote adaptive responses including antioxidant stress and amino acid metabolism. Functionally, Phospho-PERK (Thr980) serves as a central hub for cells to respond to ER stress and maintain proteostasis, and precise regulation of its levels is critical for cellular adaptation to adverse conditions; however, prolonged or irreversible PERK hyperphosphorylation may induce apoptosis and is closely associated with neurodegenerative diseases, diabetes, as well as tumor development and drug resistance, making this phosphorylation site a frequently used important biomarker for monitoring ER stress intensity and evaluating therapeutic efficacy in related diseases.